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P98174 (FGD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
FYVE, RhoGEF and PH domain-containing protein 1
Alternative name(s):
Faciogenital dysplasia 1 protein
Rho/Rac guanine nucleotide exchange factor FGD1
Short name=Rho/Rac GEF
Zinc finger FYVE domain-containing protein 3
Gene names
Name:FGD1
Synonyms:FGDY, ZFYVE3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length961 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. Ref.5

Subunit structure

Interacts with DBNL/ABP1 and CTTN. May interact with CCPG1 By similarity. Binds CDC42.

Subcellular location

Cytoplasm By similarity. Cell projectionlamellipodium By similarity. Cell projectionruffle By similarity. Cytoplasmcytoskeleton By similarity. Note: Associated with membrane ruffles and lamellipodia By similarity.

Tissue specificity

Expressed in fetal heart, brain, lung, kidney and placenta. Less expressed in liver; adult heart, brain, lung, pancreas and skeletal muscle.

Domain

The DH domain is involved in interaction with CCPG1 By similarity.

Involvement in disease

Aarskog-Scott syndrome (AAS) [MIM:305400]: A rare multisystemic disorder characterized by disproportionately short stature, and by facial, skeletal and urogenital anomalies. Some patients manifest mental retardation, attention deficit disorder and hyperactivity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.12

Defects in FGD1 are found in a patient with non-syndromal X-linked mental retardation.

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 FYVE-type zinc finger.

Contains 2 PH domains.

Ontologies

Keywords
   Cellular componentCell projection
Cytoplasm
Cytoskeleton
   DiseaseDisease mutation
   DomainRepeat
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionGuanine-nucleotide releasing factor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton organization

Inferred from direct assay Ref.5. Source: UniProtKB

apoptotic signaling pathway

Traceable author statement. Source: Reactome

cytoskeleton organization

Inferred from sequence or structural similarity. Source: UniProtKB

filopodium assembly

Inferred from direct assay Ref.5. Source: UniProtKB

multicellular organismal development

Traceable author statement Ref.5. Source: ProtInc

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

organ morphogenesis

Traceable author statement Ref.1. Source: ProtInc

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

regulation of Cdc42 GTPase activity

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement Ref.5. Source: ProtInc

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

ruffle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.5. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

small GTPase binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 961961FYVE, RhoGEF and PH domain-containing protein 1
PRO_0000080940

Regions

Domain373 – 561189DH
Domain590 – 689100PH 1
Domain821 – 921101PH 2
Zinc finger730 – 79061FYVE-type
Motif171 – 18717SH3-binding Potential
Compositional bias7 – 330324Pro-rich

Amino acid modifications

Modified residue481Phosphoserine Ref.6
Modified residue2051Phosphoserine Ref.6
Modified residue3651Phosphoserine Ref.8
Modified residue7111Phosphothreonine Ref.6
Modified residue7151Phosphoserine Ref.6

Natural variations

Natural variant2051S → I in AAS. Ref.12
VAR_019268
Natural variant3121P → L in non-syndromal X-linked mental retardation. Ref.11
Corresponds to variant rs28935498 [ dbSNP | Ensembl ].
VAR_019269
Natural variant3801E → A in AAS. Ref.12
VAR_019270
Natural variant4431R → H in AAS. Ref.12
VAR_019271
Natural variant5221R → H in AAS. Ref.9
VAR_015236
Natural variant6101R → Q in AAS. Ref.10
Corresponds to variant rs28935497 [ dbSNP | Ensembl ].
VAR_015237

Experimental info

Sequence conflict10 – 2314AGPSE…ATNPP → RRAFGARTPGHEPA Ref.1
Sequence conflict1951A → G in AAA57004. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P98174 [UniParc].

Last modified February 1, 2003. Version 2.
Checksum: 30963F7B9931E45C

FASTA961106,561
        10         20         30         40         50         60 
MHGHRAPGGA GPSEPEHPAT NPPGAAPPAC ADSDPGASEP GLLARRGSGS ALGGPLDPQF 

        70         80         90        100        110        120 
VGPSDTSLGA APGHRVLPCG PSPQHHRALR FSYHLEGSQP RPGLHQGNRI LVKSLSLDPG 

       130        140        150        160        170        180 
QSLEPHPEGP QRLRSDPGPP TETPSQRPSP LKRAPGPKPQ VPPKPSYLQM PRMPPPLEPI 

       190        200        210        220        230        240 
PPPPSRPLPA DPRVAKGLAP RAEASPSSAA VSSLIEKFER EPVIVASDRP VPGPSPGPPE 

       250        260        270        280        290        300 
PVMLPQPTSQ PPVPQLPEGE ASRCLFLLAP GPRDGEKVPN RDSGIDSISS PSNSEETCFV 

       310        320        330        340        350        360 
SDDGPPSHSL CPGPPALASV PVALADPHRP GSQEVDSDLE EEDDEEEEEE KDREIPVPLM 

       370        380        390        400        410        420 
ERQESVELTV QQKVFHIANE LLQTEKAYVS RLHLLDQVFC ARLLEEARNR SSFPADVVHG 

       430        440        450        460        470        480 
IFSNICSIYC FHQQFLLPEL EKRMEEWDRY PRIGDILQKL APFLKMYGEY VKNFDRAVEL 

       490        500        510        520        530        540 
VNTWTERSTQ FKVIIHEVQK EEACGNLTLQ HHMLEPVQRI PRYELLLKDY LLKLPHGSPD 

       550        560        570        580        590        600 
SKDAQKSLEL IATAAEHSNA AIRKMERMHK LLKVYELLGG EEDIVSPTKE LIKEGHILKL 

       610        620        630        640        650        660 
SAKNGTTQDR YLILFNDRLL YCVPRLRLLG QKFSVRARID VDGMELKESS NLNLPRTFLV 

       670        680        690        700        710        720 
SGKQRSLELQ ARTEEEKKDW VQAINSTLLK HEQTLETFKL LNSTNREDED TPPNSPNVDL 

       730        740        750        760        770        780 
GKRAPTPIRE KEVTMCMRCQ EPFNSITKRR HHCKACGHVV CGKCSEFRAR LVYDNNRSNR 

       790        800        810        820        830        840 
VCTDCYVALH GVPGSSPACS QHTPQRRRSI LEKQASVAAE NSVICSFLHY MEKGGKGWHK 

       850        860        870        880        890        900 
AWFVVPENEP LVLYIYGAPQ DVKAQRSLPL IGFEVGPPEA GERPDRRHVF KITQSHLSWY 

       910        920        930        940        950        960 
FSPETEELQR RWMAVLGRAG RGDTFCPGPT LSEDREMEEA PVAALGATAE PPESPQTRDK 


T 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor."
Pasteris N.G., Cadle A., Logie L.J., Porteous M.E.M., Schwartz C.E., Stevenson R.E., Glover T.W., Wilroy R.S., Gorski J.L.
Cell 79:669-678(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Craniofacial.
[2]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"The faciogenital dysplasia gene product FGD1 functions as a Cdc42Hs-specific guanine-nucleotide exchange factor."
Zheng Y., Fischer D.J., Santos M.F., Tigyi G., Pasteris N.G., Gorski J.L., Xu Y.
J. Biol. Chem. 271:33169-33172(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-205; THR-711 AND SER-715, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome."
Schwartz C.E., Gillessen-Kaesbach G., May M., Cappa M., Gorski J.L., Steindl K., Neri G.
Eur. J. Hum. Genet. 8:869-874(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AAS HIS-522.
[10]"A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome)."
Orrico A., Galli L., Falciani M., Bracci M., Cavaliere M.L., Rinaldi M.M., Musacchio A., Sorrentino V.
FEBS Lett. 478:216-220(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AAS GLN-610.
[11]"Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene."
Lebel R.R., May M., Pouls S., Lubs H.A., Stevenson R.E., Schwartz C.E.
Clin. Genet. 61:139-145(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NONSYNDROMAL X-LINKED MENTAL RETARDATION LEU-312.
[12]"Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients."
Orrico A., Galli L., Cavaliere M.L., Garavelli L., Fryns J.-P., Crushell E., Rinaldi M.M., Medeira A., Sorrentino V.
Eur. J. Hum. Genet. 12:16-23(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AAS ILE-205; ALA-380 AND HIS-443.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U11690 mRNA. Translation: AAA57004.1.
Z85987 Genomic DNA. Translation: CAI42222.1.
CH471154 Genomic DNA. Translation: EAW93179.1.
BC034530 mRNA. Translation: AAH34530.1.
CCDSCCDS14359.1.
PIRA55380.
RefSeqNP_004454.2. NM_004463.2.
UniGeneHs.709201.

3D structure databases

ProteinModelPortalP98174.
SMRP98174. Positions 316-786, 831-920.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108536. 4 interactions.
MINTMINT-2805047.
STRING9606.ENSP00000364277.

Chemistry

BindingDBP98174.
ChEMBLCHEMBL2862.

PTM databases

PhosphoSiteP98174.

Polymorphism databases

DMDM28202247.

Proteomic databases

MaxQBP98174.
PaxDbP98174.
PRIDEP98174.

Protocols and materials databases

DNASU2245.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000375135; ENSP00000364277; ENSG00000102302.
GeneID2245.
KEGGhsa:2245.
UCSCuc004dtg.3. human.

Organism-specific databases

CTD2245.
GeneCardsGC0XM054488.
HGNCHGNC:3663. FGD1.
HPAHPA000911.
MIM300546. gene.
305400. phenotype.
neXtProtNX_P98174.
Orphanet915. Aarskog-Scott syndrome.
PharmGKBPA28102.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295069.
HOGENOMHOG000220866.
HOVERGENHBG007506.
InParanoidP98174.
KOK05720.
OMALQMPRMP.
OrthoDBEOG7C2R0M.
PhylomeDBP98174.
TreeFamTF316247.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP98174.
CleanExHS_FGD1.
GenevestigatorP98174.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
3.30.40.10. 1 hit.
InterProIPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF01363. FYVE. 1 hit.
PF00169. PH. 2 hits.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00064. FYVE. 1 hit.
SM00233. PH. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
PROSITEPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFGD1. human.
GeneWikiFGD1.
GenomeRNAi2245.
NextBio9083.
PROP98174.
SOURCESearch...

Entry information

Entry nameFGD1_HUMAN
AccessionPrimary (citable) accession number: P98174
Secondary accession number(s): Q5H999, Q8N4D9
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 1, 2003
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM